AMOXICILLIN + CLAVULANIC ACID

Vetsuite.com Pharmacology

Amoxicillin + clavulanic acid is a combination drug that combines amoxicillin, a synthetic aminopenicillin, and clavulanic acid, a beta-lactamase inhibitor.

Amoxicillin is bactericidal and inhibits mucopeptide synthesis in the bacterial cell wall. It has good activity against a wide variety of aerobic bacteria, including E.coli, Proteus mirabilis, Salmonella, Listeria, and Hemophilus. It also has some activity against many anaerobic bacteria. Most species of Klebsiella and Pseudomonas are resistant to amoxicillin, and amoxicillin is susceptible to inactivation by beta-lactamase-producing bacteria.

To increase efficacy, amoxicillin is combined with clavulanic acid. Clavulanic acid alone has weak antibacterial activity but will competitively bind to beta-lactamase. Combining clavulanic acid with amoxicillin does not result is synergism, but strains of bacteria that are resistant to amoxicillin due to beta-lactamase activity will be susceptible to amoxicillin + clavulanic acid.

Amoxicillin + clavulanic acid is stable in gastric acid and so can be given orally. Peak levels are achieved in the serum within one to two hours following oral administration. Amoxicillin is metabolized by the kidneys and eliminated in the urine. Clavulanic acid is eliminated in the urine, feces, and expired air.

There are both veterinary and human formulations of amoxicillin + clavulanic acid, and these formulations are not equivalent. The ratio of amoxicillin to clavulanic acid varies between the formulations. The half-life of clavulanic acid is much shorter in the dog than it is in humans. For this reason, some clinical pharmacologists recommend administering amoxicillin + clavulanic acid every eight hours if treating an infection involving beta-lactamase producing bacteria.

In the United States, amoxicillin + clavulanic acid is a prescription drug.

PRECAUTIONS AND SIDE EFFECTS

Amoxicillin + clavulanic acid should not be used in animals with known hypersensitivity or allergy to the drug or other penicillins. Because of potential cross-reactivity, animals allergic to ampicillin may also be hypersensitive or allergic to cephalosporins, though this is controversial. Only about 15 percent of people allergic to penicillins have been found to be allergic to cephalosporins.

The most common side effects associated with amoxicillin + clavulanic acid are gastrointestinal upset: Vomiting and anorexia may occur. In cats, diarrhea is relatively common. As with other penicillins, chronic administration of high doses of amoxicillin + clavulanic acid has been associated with neurologic signs, including ataxia.

Be aware that Kirby-Bauer susceptibility testing is performed using Augmentin® disks. Since the ratio of clavulanic acid is different in the human vs. animal formulation, the results of susceptibility testing may not be accurate in animals.

DRUG INTERACTIONS

When used concurrently with aminoglycoside antibiotics, synergism may occur against enterococci and many other gram-negative bacteria. When high doses of amoxicillin + clavulanic acid are used concurrently with rifampin, antagonism can occur.

HOW AMOXICILLIN + CLAVULANIC ACID IS SUPPLIED

Amoxicillin + clavulanic acid is available in a variety of concentrations and with various proportions of amoxicillin and clavulanic acid. The veterinary tablets are available as:

Amoxicillin + clavulanic acid tablets and powder should be stored at room temperature. Once reconstituted, the solution should be refrigerated and is stable for 10 days.

Amoxicillin is degraded by moisture; therefore, the blister packs should not be opened until it is time to administer the medication. Amoxicillin + clavulanic acid should not be stored in wet or humid areas.

DOSING INFORMATION

The dose of amoxicillin + clavulanic acid is 10 to 25 mg/kg PO two or three times a day. Since the half-life of clavulanic acid is relatively short in dogs and cats, some pharmacologists recommend that amoxicillin + clavulanic acid be administered three times a day for most infections that are resistant to amoxicillin alone. Urinary tract infections can effectively be treated with twice a day therapy.

Doses of amoxicillin + clavulanic acid are determined according to the amoxicillin content of the tablet since ratios of clavulanic acid in the preparation may vary.